Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel

Abstract

Background Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance. Methods We retrospectively reviewed data obtained from December 20, 2020, to May 31, 2021, regarding all cases of myocarditis and categorized the information using the Brighton Collaboration definition. We analyzed the occurrence of myocarditis by computing the risk difference for the comparison of the incidence after the first and second vaccine doses (21 days apart); by calculating the standardized incidence ratio of the observed-to-expected incidence within 21 days after the first dose and 30 days after the second dose, independent of certainty of diagnosis; and by calculating the rate ratio 30 days after the second dose as compared with unvaccinated persons. Results Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis. Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable. The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal. The overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval [CI], 1.33 to 2.19), with the largest difference among male recipients between the ages of 16 and 19 years (difference, 13.73 per 100,000 persons; 95% CI, 8.11 to 19.46). As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20). The rate ratio 30 days after the second vaccine dose in fully vaccinated recipients, as compared with unvaccinated persons, was 2.35 (95% CI, 1.10 to 5.02); the rate ratio was again highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637. Conclusions The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.

Three doses of COVID-19 mRNA vaccination are safe based on adverse events reported in electronic health records

“…We observed no significant increase in EHR reporting of severe adverse events after the 3 rd dose compared with after the 2 nd dose, with incidence comparable with previous literature. 16,17 The observed increase in adverse events compared with earlier doses could be due to a stronger response elicited by the 3 rd dose, comparable to what was observed for the 2 nd dose compared with the 1 st dose. 1,2,33 Further studies are needed to explore whether the 3 rd vaccine dose does indeed induce a stronger immune response.…”

“…Extensive research has shown that the standard 2-dose regimen of mRNA-based COVID-19 vaccines is relatively safe. Although severe adverse events such as anaphylaxis, 15 myocarditis, 16,17 and blood clotting, [18][19][20][21][22] have been reported after COVID-19 vaccination, these are rare and the benefit of vaccination is deemed to outweigh the potential risks. The most common adverse reactions occur immediately post vaccination 23 and are relatively mild, including headache, fatigue, pains, low-grade fever, and nausea.…”

Anti-SARS-CoV-2 vaccination does not induce the formation of autoantibodies but provides humoral immunity following heterologous and homologous vaccination regimens: Results from a clinical and prospective study within professionals of a German University Hospital

“…However, it represents a significant gap in our knowledge that despite the connection of severe COVID-19 infections and the occurrence of autoantibodies, no systematic clinical study assessing whether COVID-19 vaccination also triggers the production of autoantibodies has been published yet. Such an investigation would be of significant interest especially in view of very recent studies reporting myocarditis after mRNA vaccination especially in younger (< 30 years) male individuals (Barda et al 2021;Mevorach et al 2021;Verma et al 2021;Witberg et al 2021). To address this important question, we here analyzed anti-SARS-CoV2 and autoantibody responses in healthcare workers before and after applying heterologous and homologous vaccination protocols against COVID-19.…”

Boosters appear effective, but are they always needed?

“…A study from Israel has reported a higher risk of myocarditis after the second dose, with a rate ratio of 2·35 (95% CI 1·10–5·02) compared with unvaccinated individuals. 9 Is the benefit to risk ratio of the third dose different for older and younger individuals? Concerns exist regarding vaccine-induced thrombotic thrombocytopenia in younger recipients of virus vector vaccines.…”